2篇
您的检索式：作者名="Peter Robin Shepherd"
|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | Identification, structure modification, and characterization of potential small-molecule SGK3 inhibitors with novel scaffolds显示文摘The serum and glucocorticoid-regulated kinase (SGK) family has been implicated in the regulation of many cellular processes downstream of the PI3K pathway. It plays a crucial role in PI3K-mediated tumorigenesis, making it a potential therapeutic target for cancer. SGK family consists of three isoforms (SGK1, SGK2, and SGK3), which have high sequence homology in the kinase domain and similar substrate speci?city with the AKT family. In order to identify novel compounds capable of inhibiting SGK3 activity, a high-throughput screening campaign against 50,400 small molecules was conducted using a fuorescence-based kinase assay that has a Z' factor above 0.5. It identiifed 15 hits (including nitrogen-containing aromatic, favone, hydrazone, and naphthalene derivatives) with IC50 values in the low micromolar to sub-micromolar range. Four compounds with a similar scaffold (i.e., a hydrazone core) were selected for structural modi?cation and 18 derivatives were synthesized. Molecular modeling was then used to investigate the structure-activity relationship (SAR) and potential protein–ligand interactions. As a result, a series of SGK inhibitors that are active against both SGK1 and SGK3 were developed and important functional groups that control their inhibitory activity identified. | Grace Qun Gong Ke Wang Xin-Chuan Dai Yan Zhou Rajesh Basnet Yi Chen De-Hua Yang Woo-Jeong Lee Christina Maree Buchanan Jack Urquhart Flanagan Peter Robin Shepherd Ying Chen Ming-Wei Wang | 2018 | Acta Pharmacologica Sinica2018，39，12： | 1 |
| 2 | High-throughput screening campaigns against a PI3Kα isoform bearing the H1047R mutation identified potential inhibitors with novel scaffolds显示文摘phosphatidylinositol 3-kinase (PI3K ) 小径包括房间生长,新陈代谢,和转变涉及许多细胞的功能。因此,这条小径的 Hyperactivation 贡献 tumorigenesis PI3K 是为 anticancer 的一个主要目标药发现。因为 PI3K isoform 主要在癌症被含有,我们进行了一高产量 ? 屏蔽(HTS ) 对忍受 H1047R 变化的这 isoform 用 3 步 PI3K 同质的解决时间的荧光试金竞选。288,000 合成、自然的导出产品的混合物的一个总数被屏蔽并且哪个,我们识别了被把预言的有约束力的模式,到已知的平底锅试金干扰混合物的关系和以前的描述看作一个类脂化合物 kinase 禁止者进一步选择的 124 起始的点击。24 混合物的一个总数然后为集中依赖者回答被测试。这些点击混合物提供能潜在地被优化创造新奇 PI3K 禁止者的新奇脚手架。 | Jia Wang Grace Qun Gong Yan Zhou Woo-Jeong Lee Christina Maree Buchanan William Alexander Denny Gordon William Rewcastle Jackie Diane Kendall James Michael Jeremy Dickson Jack Urquhart Flanagan Peter Robin Shepherd De-Hua Yang Ming-Wei Wang | 2018 | Acta Pharmacologica Sinica2018，39，11： | 0 |
您所在的机构暂未开通此部分的功能，请联系管理员